Epitope affinity for MHC class I determines helper requirement for CTL priming

Franco, Alessandra; Tilly, Darcie A.; Gramaglia, Irene; Croft, Michael; Cipolla, Laura; Meldal, Morten; Grey, Howard M.

doi:10.1038/77827

Cited by 75 publications

(63 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the correlation shown here between T cell help, frequency of long-term memory CTLp and protection is compelling evidence of the longterm immunological advantage offered by T cell help during priming. Obviously, these considerations are only relevant to the long-term consequences of priming by epitope-based immunization [31], including those utilizing helper-independent analogue CTL peptides [32]. Whether or not in our model high CTLp frequencies require persistent antigen [33] was not studied, but one cannot exclude that transgenic Ig may be stored on follicular DC as a long-term antigen depot [34].…”

Section: Discussionmentioning

confidence: 99%

Role of T cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus

et al. 2003

View full text Add to dashboard Cite

We report on the induction of primary and long-term memory cytotoxic T lymphocyte (CTL) responses against the nucleoprotein of the influenza virus A/PR8/34 in mice immunized with plasmid DNA targeted to B lymphocytes in the spleen. We found that the magnitude of the CTL response and the size of the pool of memory CTL was greater when the CTL response was induced in presence of T cell help. Interestingly, immunization with a signal sequencecompetent transgene was markedly superior to immunization with a transgene lacking the endoplasmic reticulum (ER) targeting sequence, in inducing CTL. We also found a correlation between in vivo protection from lethal virus challenge and (1) the availability of T cell help and (2) ER targeting. Immunization of dendritic cell-deficient mice suggests that B lymphocytes function as antigen-presenting cells in this model of immunization. Collectively, the results suggest that somatic transgene immunization is a conceptually new approach to induce effective anti-viral CTL responses and to assess the parameters critical for long-lasting and protective CTL responses in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of T cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus

et al. 2003

View full text Add to dashboard Cite

show abstract

“…This requirement may reflect the low affinity of the CD8 ϩ repertoire that is available for response to a self-Ag. It was recently demonstrated that one factor that is determinative of CD4 dependence of a CD8 response is that stability of the peptide-class I complex (38). It is likely that TCR affinity plays a similar role in determining the stability of the TCR-peptide-MHC complex.…”

Section: Discussionmentioning

confidence: 99%

CTLA-4 Blockade Enhances the CTL Responses to the p53 Self-Tumor Antigen

Hernández

Sherman

2001

The Journal of Immunology

View full text Add to dashboard Cite

p53 is an attractive target for cancer immunotherapy because it is overexpressed in a high proportion of many different types of tumors. However, it is also expressed in normal tissues and acts as a toleragen in vivo. Previously, detailed examination of the repertoire specific for the murine p53261–269 epitope in conventional and p53-deficient mice demonstrated that because of expression of p53, the CD8+ T cells that respond to this epitope express low-affinity TCRs. It has been reported that tolerance to tumor Ags can be broken by in vivo administration of anti-CTLA-4 mAb. With the goal of overriding tolerance and achieving optimal activation of p53-specific CTL, the current study has assessed the effect of anti-CTLA-4 mAb on the p53-specific repertoire. It was found that blockade of CTLA-4 engagement at the time of antigenic stimulation induced a vigorous amplification of the CTL responses to p53 as well as proportionate expansion of the memory T cell pool. This effect was dependent on the presence of CD4+ T cell help and correlated with an enhancement of helper function. However, anti-CTLA-4 treatment did not enhance the avidity of the resultant p53-specific CTL populations and, therefore, could not reverse this important consequence of tolerance.

show abstract

“…They include antigen-specific features, such as nature and concentration of the immune-stimulating materials [46] or T-cell intrinsic characteristics, such as antigen precursor frequency [47].…”

Section: Discussionmentioning

confidence: 99%

CD40 ligand‐expressing recombinant vaccinia virus promotes the generation of CD8⁺ central memory T cells

et al. 2015

View full text Add to dashboard Cite

Central memory CD8 + T cells (T CM ) play key roles in the protective immunity against infectious agents, cancer immunotherapy, and adoptive treatments of malignant and viral diseases. CD8+ T CM cells are characterized by specific phenotypes, homing, and proliferative capacities. However, CD8 + T CM -cell generation is challenging, and usually requires CD4 + CD40L + T-cell "help" during the priming of naïve CD8 + T cells. We have generated a replication incompetent CD40 ligand-expressing recombinant vaccinia virus (rVV40L) to promote the differentiation of human naïve CD8 + T cells into T CM specific for viral and tumor-associated antigens. Soluble CD40 ligand recombinant protein (sCD40L), and vaccinia virus wild-type (VV WT), alone or in combination, were used as controls. Here, we show that, in the absence of CD4 + T cells, a single "in vitro" stimulation of naïve CD8 + T cells by rVV40L-infected nonprofessional CD14 + antigen presenting cells promotes the rapid generation of viral or tumor associated antigen-specific CD8 + T cells displaying T CM phenotypic and functional properties. These observations demonstrate the high ability of rVV40L to fine tune CD8 + mediated immune responses, and strongly support the use of similar reagents for clinical immunization and adoptive immunotherapy purposes.Keywords: Antigen presenting cells r Central memory T cells r CD40-CD40L r CD4 + T cells r CD8 + T cells r Immunological memory r Vaccinia virus Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionGeneration of immunological memory represents a key tenet of the adaptive immune system. Memory T cells display the exquisite Correspondence: Dr. Paul Zajac e-mail: paul.zajac@usb.ch ability to respond to previously experienced antigens with clonal expansion and with the rapid elicitation of multiple effector function [1]. However, the origin of memory CD8 + T cells is still debated, particularly concerning the relationship between effector and memory cells [2].Current understanding is consistent with the "one cell, multiple fates" model postulating that memory and effector T cells C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2016. 46: 420-431 Immunomodulation 421 may arise from single naïve CD8 + T-cell precursor undergoing asymmetric division originating two daughter cells with different cell fates [3]. Alternatively, a linear differentiation model proposes that memory CD8 + T lymphocytes may derive from effector cells surviving the contraction phase of the primary immune response [4]. Memory compartment encompasses lymphocyte subpopulations characterized by different phenotypes, functional properties, and anatomic locations. Two main subsets, central (T CM ) and effector memory (T EM ) lymphocytes, displaying a differential expression of homing and chemokine receptors have consistently been identified [5,6].Notably, T CM are characterized by high proliferative potential in response to antigen stimulation and...

show abstract

Epitope affinity for MHC class I determines helper requirement for CTL priming

Cited by 75 publications

References 45 publications

Role of T cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus

Role of T cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus

CTLA-4 Blockade Enhances the CTL Responses to the p53 Self-Tumor Antigen

CD40 ligand‐expressing recombinant vaccinia virus promotes the generation of CD8⁺ central memory T cells

Contact Info

Product

Resources

About

Epitope affinity for MHC class I determines helper requirement for CTL priming

Cited by 75 publications

References 45 publications

Role of T cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus

Role of T cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus

CTLA-4 Blockade Enhances the CTL Responses to the p53 Self-Tumor Antigen

CD40 ligand‐expressing recombinant vaccinia virus promotes the generation of CD8+ central memory T cells

Contact Info

Product

Resources

About

CD40 ligand‐expressing recombinant vaccinia virus promotes the generation of CD8⁺ central memory T cells